The future of food allergy: Challenging existing paradigms of clinical practice

The field of food allergy has seen tremendous change over the past 5–10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food‐allergic patients and their families. Additionally, novel diagnostic tools are making their way into clinical practice with the goal to reduce the need for food challenges and assist physicians in the—often complex—diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision‐making has become a key part of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.


| INTRODUC TI ON
The landscape of food allergy has changed significantly over the past 5-10 years, with traditional approaches to diagnosis and management giving way to new ways of clinical practice. Many exciting developments have taken place including new epidemiological trends, novel diagnostics, therapies and the incorporation of shared decision-making into daily practice. In this review, we aim to examine recent changes and envision the evolution of food allergy over the next decade.

| NE W TRENDS IN FOOD ALLERGY PRE VALEN CE
Food allergy is overestimated using methods such as surveys of self-reported symptoms or those based on IgE sensitization. A Scandinavian cohort study of 3623 children reported a cumulative incidence of food allergy of 35% by age 2 years, based on parental reports. 1 Two large surveys in the USA suggested a prevalence of 7.6% in children and 10.8% in adults. 2,3 However, parental-and selfreport significantly overestimate the rate of food allergy. For example, a recent review concluded that confirmed milk allergy is 15-to 20-fold less frequent than parentally reported symptoms. 4 Similarly, a European systematic review suggested a self-reported prevalence between 13.1% and 19.9%, with serum IgE sensitization of 16.6% and skin testing of 5.7%, with only 0.8% based on oral food challenge (OFC). Lipid transfer protein allergy has emerged as the most common cause of primary food allergy and food-induced anaphylaxis in older children and adults residing in Southern European countries (Mediterranean and Atlantic areas). 5 Australian data using OFC-based diagnosis estimated a rate of 10% for raw egg and 3% for peanut in children aged 1 and 4%-5% for older children and teenagers. [6][7][8] Birth cohorts from Europe identified significant country-to-country variability in individual food allergies. [9][10][11] In developing countries, data are limited. Surveys from China and India suggested 10-fold differences in rates of IgE-mediated allergy; 0.14% in India and 1.5% in Hong Kong. 12 Several Singaporean studies identified peanuts as a common allergen. 13,14 In contrast, prior Singaporean studies identified no cases of peanut allergy, suggesting a change in dietary or other social patterns. 14,15 The patterns of food allergy in developing countries may elucidate the link between progressive urbanization and the development of food allergies; South African data suggested a fivefold discrepancy between rural and urban rates of food allergy. 16 Interestingly, while urbanization may alter infectious and environmental allergen exposures and feeding behaviour, immigration may represent a similar phenomenon. In Australia, children of Asian immigrants appear to have a significantly increased risk of developing food allergies despite low rates in their countries of origin, 17,18 with similar data reported from Canada. 19 Despite a better understanding of early introduction to prevent food allergy, few studies have evaluated changing patterns after the dissemination of prevention guidance. Following implementation in Australia, the rates of hospital admissions due to anaphylaxis increased in infants, possibly consistent with elevated rates of early exposure. 20 However, there was no evidence of a fall in the prevalence of peanut allergy when comparing rates of positive OFC to peanuts across two birth cohorts, despite advice relating to early introduction being implemented. 21 This phenomenon may be related to the significant immigration of Asian families with increased rates of peanut allergy and delayed introduction. 20 The epidemiology of food allergy is evolving as social, behavioural and dietary practices change. Moving forward, robust methods are needed to identify the true nature of these trends.

| CHALLENG ING THE GOLD S TANDARD FOR IMPROVED D IAG NOS IS OF FOOD ALLERGY
The gold-standard diagnostic test for food allergy is an OFC.
However, OFCs can result in allergic reactions of unpredictable severity and there is often limited capacity, resulting in long waiting times. 22 of medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments as well as the evolution of the field of food allergy in the next decade.

K E Y W O R D S
food allergy, novel diagnostics, prevention, shared decision-making, therapy Over the years, allergists have used the presence of specific IgE as evidence of food allergy, averting OFC if IgE testing corroborated the clinical history or the levels were above certain cut-offs. 23 Optimal cut-offs and their diagnostic performance are dependent on a variety of factors and may be specific to the patient population, geographical location and centre where they were generated, among other factors. 24 One of the advances in diagnostics has been the higher specificity of specific allergen components, such as Ara h 2 for peanut, Cor a 14 for hazelnut, Ana o 3 for cashew and Ses i 1 for sesame. [25][26][27][28] Figure 1 illustrates the main in vitro tests that are available clinically or in development to document the presence of allergenspecific IgE. IgE testing has evolved from using a mixture of proteins in extracts to individual allergen molecules to short peptides within the allergen molecules. The use of smaller parts of the allergen source can increase specificity but limits the areas for IgE binding and thus can incur false negative results. One strategy to reduce the false negative rate is to test for IgE to allergen components (or peptides) alongside IgE to the extract derived from the allergen source.
Another novelty is the development and validation of cellular tests, such as the basophil activation test (BAT), the mast cell activation test (MAT) and the determination of IgE binding to epitopecontaining peptides, using peptide microarray or a bead-based assay (BBEA). [29][30][31][32][33][34][35][36][37][38][39][40] This testing mode can be more specific than IgE to the whole allergen, as was demonstrated for peanut allergy with an increase in 7.7% specificity and 7.7% PPV compared to Ara h 2-sIgE alone. 41 However, testing for linear peptides inevitably misses conformational epitopes, which are important for antibody binding. IgE to epitope-containing peptides seems to be particularly informative with IgE to linear peptides being associated with persistent milk/ egg allergy and reaction to the baked forms of these foods. 42,43 BAT and MAT are cellular functional assays that include all the immune components of acute allergic reactions and therefore can reproduce more closely the clinical phenotype of the patients than assays that measure IgE titres. [44][45][46][47] For peanut allergy, BAT has shown 97% accuracy, 98% sensitivity and 96%specificity in an initial study and 83% sensitivity and 100% specificity in a large external validation cohort, demonstrating its value in confirming peanut allergy 29,44,45 (Table 1).
In the future, tests using peptides and BAT are making the transition to clinical practice as the scientific evidence accumulates to support their diagnostic utility and cost-effectiveness. 48 Regulators recognize the importance of reducing the need for OFCs, improving the care to patients and the efficiency of testing and introducing foods in the diet.

| AN OUN CE OF PRE VENTI ON IS WORTH A P OUND OF CURE
Benjamin Franklin stated that 'an ounce of prevention is worth a pound of cure'. In the last 10 years, several ground-breaking studies showed that early (under 6 months of age) introduction of allergenic foods prevents the development of food allergies, especially in children that are at high risks, such as those with eczema [49][50][51][52][53] These studies have resulted in international guideline changes by several allergy societies. [54][55][56][57][58][59] Although some differences exist between different guidelines (Table 2), they all recommend not delaying the introduction of allergenic foods beyond 6-12 months. The remaining questions include the dose, frequency and duration required to achieve oral tolerance induction, the role of maternal dietary exposure (or the triple exposure hypothesis), what adjuncts may help with avoiding Th2 skewing (vitamin D, immunization) and the role of other environmental (e.g., detergents, pollution) and nutritional factors. [60][61][62][63][64][65] F I G U R E 1 IgE titres to food extracts and to individual allergens are widely available. IgE to peptides and the basophil activation test (BAT) is making the transition to clinical practice. Figure built with Biorender.
Limitations of early introduction of food allergens include the feasibility of introducing multiple allergenic foods into an infant's diet. Additional challenges, such as sleep deprivation, feeding difficulties and concerns about allergic reactions may also raise limitations to the implementation of early introduction of allergenic foods. 66,67 Several studies have shown that breastfeeding duration is not adversely impacted by early introduction of solids. 68,69 Most allergenic foods are high in protein, raising concern that a highprotein diet may lead to obesity; however, high-dose, early introduction of allergenic foods has not been shown to increase BMI, triceps skinfold thickness or abdominal circumference. 51,68 Implementation of the guidelines for food allergy prevention has been challenging. [70][71][72] Although peanut introduction in the first year of life in Australia increased from 28.4% to 88.6%, the rates of peanut allergy did not significantly reduce (3.1% in 2007-2011 vs. 2.6% 2018-2019, p = 0.26). The paper did not report on the duration or frequency of peanut intake, or the way in which peanut was introduced (e.g., boiled, roasted, in a matrix), only timing of peanut introduction. Earlier introduction (before 6 vs. before 12 months of age) was significantly associated with a reduction in peanut allergy among infants of Australian ancestry age 12 months compared with age 6 months or younger: adjusted odds ratio, 0.08 [05% CI, 0.02-0.36] but not significant among infants of East Asian ancestry (p for interaction = 0.002). 21,73 The future of food allergy prevention will be multifactorial. The role of emollient therapy in preventing eczema, thus hopefully preventing transcutaneous sensitization and food allergy, has shown TA B L E 1 In vitro diagnostic tests and their diagnostic performance using peanut allergy as an example.

Description of tests
Output of tests mixed results and requires further investigation. [74][75][76] Early proactive treatment of moderate to severe eczema has been shown to prevent hen's egg allergy at 6 months of age by 10% in the PACI (Prevention of Allergy via Cutaneous Intervention) study 77 ; however, this also led to significant growth retardation. The PACI study included 14 days of twice daily whole body and face topical steroid application followed by 15-21 weeks of twice weekly, twice daily whole body and face topical steroid application (including non-affected areas). The SEAL study (Stopping Eczema and Allergy Study: https://clini caltr ials.gov/ct2/ show/NCT03 742414) is ongoing and there is at present insufficient evidence to implement this approach in clinical practice. The role of pre and probiotics in conjunction with oral tolerance induction is also being evaluated. [78][79][80] Feasibility, acceptability and shared decision-making with parents will be crucial for implementing any future strategy to prevent food allergy. Getting sound evidence is paramount for including the recommendations as public health guidance. Translation in adequate language to patients and caregivers of the available evidence would facilitate understanding of the options, feasibility and acceptance.

| N UTRIENTS AND THE MICROB I OME
Nutrition can affect microbiome composition and function, affecting immune indices and allergy outcomes. Current research links TA B L E 2 Guidance for allergenic food introduction by different allergy societies.

Guidance Population/recommendations Age to introduce
European Academy of Allergy and Clinical Immunology (EAACI), 2021, Europe Suggests introducing well-cooked, but not raw egg or uncooked pasteurized, egg into the infant diet as part of complementary feeding from 4-6 months. In populations where there is a high prevalence of peanut allergy, suggests introducing peanuts in an age-appropriate form as part of complementary feeding from 4-6 months.  82 whereas children who develop egg allergy present with higher microbial diversity. 84 Differences also exist between children who develop milk tolerance compared with those who fail. Children with higher gut microbial diversity appear to develop tolerance sooner than those with lower diversity. 81 Infants who are sensitized to food allergens also have a different gut microbiome profile than non-sensitized infants in terms of species studied. In a Canadian study, children sensitized to food allergens had a higher abundance of Proteobacteria and those not sensitized had a higher abundance of Bacteroides. 85 Differences in the gut microbiome are also apparent in food-allergic adults and non-allergic controls. Hua et al. showed that faecal microbiota richness was lower in those with peanut allergies. 86 Microbial taxa also differed between food-allergic and non-food-allergic adults, with higher levels of Bacteroidales and reduced Clostridiales taxa in nut-allergic individuals. 86 Dietary intake may mediate the gut microbiome outcomes through the individual nutrient intake, food intake and the overall diet pattern. 65,87 Diet diversity may affect all aspects of the gut microbiome by providing more fibre and nutrients. Diet diversity in infancy and reduced odds of food allergy in childhood were reported by the PASTURE study. 88 Roduit et al. demonstrated that increased diet diversity in the first year of life was associated with reduced odds of food allergy by 6 years. A diet rich in fruit, vegetables, fish and yoghurt in infancy has been associated with the production of butyrate, a short-chain fatty acid (SCFA), in the gut. 88 A Korean study reported that higher diet diversity scores at 3, 4 and 5 months of age were associated with increased microbial diversity at 6 months. Gene expression of pro-inflammatory and Th2-cytokines and chemokines, IL-4, IL-5, IL-6 and IL-8, were higher among infants with lower diet diversity scores than those with higher diet diversity scores. 89 High-risk infants with a higher food allergen diversity score at 5 months of age showed a reduced gene expression of IL-13. 89 A recent study in pregnant women showed that increased healthy diet diversity in pregnancy was associated with reduced offspring allergy outcomes defined as 'all allergies excluding wheeze' by 4 years, but microbiome data were not available. 90  Fibre is often considered the nutrient with the greatest potential to change the gut microbiome. However, a recent EAACI systematic review could not identify any studies on fibre intake and food allergy outcomes, although the authors highlighted the importance of fibre on the microbiome and its effects on immune regulation. 92 Other nutrients that have been shown to modulate the gut microbiome include total fat, protein and carbohydrates, but their effects on food allergy outcomes have not been evaluated. 93 Nutrients do not exist in isolation and using a whole diet approach to better understand the role of overall nutrition on the microbiome composition and function is essential. In the future, more rigorous studies are required to further examine associations between diet patterns and nutrient intake on both the microbiome and food allergy outcomes.

| FOOD ALLERGY THER APIE S -A B RI G HT FUTURE AHE AD
The landscape of food allergy therapy has seen tremendous change over the previous 5-10 years, with active management options, such as food immunotherapy, providing patients with alternatives to strict food avoidance. Large, randomized-controlled trials have confirmed the efficacy and safety of these new approaches as well as the nutritional benefits following successful therapy. [94][95][96][97][98][99][100] In addition, the ability of immunotherapy to raise the allergenic threshold of reactivity has resulted in protection from accidental exposures, reduction in allergic reaction severity and improved quality of life for foodallergic patients and their families. [100][101][102][103][104][105][106] The EAACI guidelines on food immunotherapy note that there is a substantial benefit for patients undergoing OIT for cow's milk, hen's egg and peanut allergy. Despite adverse events frequently reported, few subjects discontinue food immunotherapy due to these. Biologics present significant advantages since they are not foodspecific, their dosing is intermittent (rather than daily), they have a good safety profile and may achieve control of co-existing allergic comorbidities. 109 However, their long-term use has not been systematically examined, the optimal time for discontinuation remains unknown, adverse events reduction compared to single OIT has been controversial, and cost and access limitations remain a barrier. 101,[110][111][112][113][114] Biologics require further investigation and longer-term studies to evaluate outcomes after they have been discontinued (Table 3). TA B L E 3 Novel therapies for food allergy: benefits, considerations and risks.

Considerations and risks
Oral immunotherapy (OIT) 94,95,100,[191][192][193][194][195][196] • Desensitization (rise in the allergic threshold of reactivity) in the majority of food-allergic individuals within 6-12 months. • Protection from 'trace' a exposures and larger accidental exposures (depending on the level of desensitization) • Improved quality of life for patients and families. • FDA-approved products available in the US and some EU countries.
• Anaphylaxis: ~14% • Not a cure for the food allergy, but some patients are able to 'free-eat' following desensitization to large amounts and sustained unresponsiveness. There is also potential for remission in young children. • Addition of the probiotic provides the greatest benefit to children aged 1-5 years with a reduced withdrawal rate (5% in PPOIT and 14% in OIT) • The addition of probiotic results in a 30%-50% reduction in GI symptoms, systemic reactions, and moderate to severe adverse events in children aged 1-5 years • No difference in efficacy (desensitization or sustained unresponsiveness) • Both interventions provide similar improvements in quality of life a 'Trace' is defined as a very small quantity, especially one too small to be accurately measured.

| C AN WE PRED IC T THE S E VERIT Y OF FOOD -ALLERG I C RE AC TI ON S AND RIS K-S TR ATIF Y PATIENTS?
Defining the 'mild' food allergy patient phenotype has proved challenging. One step in this process is to evaluate various biomarkers or patient-specific factors as predictive markers of the severity of reactions during OFCs. 44,[121][122][123][124][125][126][127][128] While some biomarkers including food-specific IgE level, BAT, component-resolved diagnostics and epitope mapping have been studied in this regard, no test has been well validated to predict the risk of severity of reaction in real-world settings and some are not readily available. This is partly because the severity of food-allergic reactions in the real world is dependent on too many factors beyond these biomarkers (e.g., the allergen itself, dose ingested, comorbidities, external cofactors, such as exercise or viral illness). 129 Based on this, the most recent European guidelines do not recommend using testing to predict severity. 100 Another attempt to classify risk is by evaluating patient cohorts of severe and fatal reactions and examining common findings in these cohorts. [130][131][132][133][134] For food-induced fatal anaphylaxis, some reported common findings to include young adults with asthma, delayed administration of epinephrine, and certain trigger foods (e.g., peanut, tree nuts, milk). 130 Patients who fall into these categories may be considered at higher risk. However, these studies fail to compare risk factors in large cohorts. For example, while many patients with fatal food-allergic reactions do have asthma, it may not be any higher than the number of food-allergic patients with asthma that do not have severe reactions. However, given that asthma is a modifiable risk factor, striving to achieve control of asthma (if a food-allergic patient has asthma) is a reasonable approach to attempt to mitigate the risk of severe reactions. 100 Finally, the absence of the above 'risk factors' does not mean patients are free from risk.
It seems inherently difficult to successfully risk-stratify foodallergic patients, and it is unlikely there will ever be a fool-proof risk-stratification algorithm to correctly classify every single patient.
More likely, if there were a data-driven algorithm, it would require a shared decision-making discussion to explain the risk of severe reaction based on history and lab data, evaluate the patient's risk tolerance and subsequently decide on management/therapy options, even if the risk of severe reaction were calculated at an extremely low level (Figure 2).
There have been attempts recently to clarify and harmonize scores and definitions of severity. 135,136 While these may help in clinical and research settings, they are unlikely to change the biggest issue of anaphylaxis at the patient level: the delay in or failure to use epinephrine appropriately. Reasons for this include fear of needle, fear of side effects of medication, cost of device, lack of access to epinephrine, not having device available at time of reaction, etc 137 One area of research that can practically affect these issues in the coming years may be through alternate epinephrine delivery routes. Currently, intranasal and sublingual routes are the most researched. 138 In the future, better risk stratification and alternative delivery systems of epinephrine will hopefully lead to a more efficient approach in managing food-allergic patients.

| US ING ALLERG EN THRE S HOLDS TO INFORM PATIENT C ARE
With the increasing use of OFCs to inform diagnosis, there is now increasing understanding relating to the concept of patient allergen thresholds-that different individuals need to be exposed to variable amounts of their trigger to elicit allergic symptoms. For example, over 50% of peanut-allergic individuals need to consume at least half a peanut before having an objective allergic reaction. Many allergic F I G U R E 2 Suggested future schematic of food allergy management in a known food-allergic patient, based on risk severity and alternate forms of epinephrine.  (Figure 3).

Patient Intrinsic Factors
Population-based, dose-distribution curves have been published for many allergens. 140  These data can impact the future management of patients in the following ways:

| Low-dose challenges
Single-dose, low-dose challenges-where the individual is given a small (typically ED 05 ) exposure-have been published for peanut and cow's milk. 144 Demonstrating that an allergic individual does not react to tiny amounts of food protein can be reassuring and may improve quality of life. 144 A recent survey reported significant interest from food-allergic individuals and their families to undergo such challenges as routine. 145 When adopting this approach, it is important to consider sensitivity and severity separately. There is a complex and poorly understood association between the dose needed to trigger symptoms and the severity of resulting symptoms. 129,146 Both logic and experience from food challenges would dictate that symptom intensity increases with increasing amounts of allergen exposure; this would suggest that those who are more sensitive (react to lower doses) are at greater risk of severe reactions if exposed to higher doses of the allergen. However, in an analysis of 734 DBPCFC, dose predicted only 4.4% of the variance in reaction severity, that is dose was not an important factor in predicting severity. 147 Likewise, for peanut allergy, individuals with a history of anaphylaxis do not have a different distribution of reaction thresholds at DBPCFC compared to those with only prior mild reactions. 148 Irrespective, tolerance to an ED 05 exposure can alleviate anxiety: in our experience, at least 50% of food-allergic individuals (or their carers) consider themselves as at risk of anaphylaxis to very low (ED 05 ) exposures, despite only 0.25% of them actually being so. Furthermore, if a regulated and threshold-based approach can be applied to food labelling, then single, low-dose challenges will become increasingly important in patient management.

| Inform precautionary allergen labelling
The first scheme to use thresholds (derived from population-based, dose-distribution curves for eliciting doses) to inform precautionary allergen labelling on prepacked foods was the VITAL® Program developed by the Allergen Bureau of Australia and New Zealand. This approach has now been adopted in a recent Expert Consultation undertaken by the Food and Agricultural Organization of the United Nations/World Health Organization and is being considered for implementation at a global level. 149 If successful, it will result in a more targeted and rational approach to allergen labelling, helping allergic consumers make informed and safe food choices.

F I G U R E 3
Estimates refer to the occurrence of allergic symptoms at ED 05 levels of exposure in food-allergic individuals. ED 05 , the amount of allergen expected to cause objective symptoms in 5% of the population with that allergy. Figure

| Individualize patient management
Individuals who need higher levels of allergen exposure to induce symptoms may be able to take a less restrictive approach to allergen avoidance-for example, eating foods manufactured on shared production lines. 150 This approach would require an assessment of the threshold through a food challenge, although surrogate tests (BAT, epitope mapping) currently under development may be useful as an alternative or to inform those who demonstrate a lack of reactivity to low allergen exposures. 151 Allergic consumers would need to be advised how to undertake their own informed risk assessment, which considers the potential for a lapse in allergen management on the part of the food business and the need for patients to self-manage any resulting accidental reaction.

| Patient selection for food allergy desensitisation
Studies indicate that higher-threshold reactors appear to have better outcomes from desensitization, including remission. 152 Indeed, many individuals could undergo immunotherapy without the need to consume small doses; for example, 40-50% of peanut-allergic individuals can tolerate a whole peanut kernel without significant subjective or objective symptoms. Such individuals, once identified, could proceed to oral immunotherapy using an expedited protocol with higher initial doses 150 potentially achieving an ad-lib consumption status of their food allergen.

| THE PATIENT ' S VOI CE IN FOOD ALLERGY CHOICE S: S HARED DECIS ION -MAKING
There has been a robust expansion of incorporation of shared decision-making into food allergy practices in recent years. Briefly, shared decision-making (SDM) is a process whereby the patient/ family and the clinician meet to mutually explore the risks, benefits, alternatives, and other considerations regarding a medical decision.
The exchange of information between parties allows the patient/ family to clarify their values and preferences regarding a diagnostic, treatment or management option, with the goal to make an informed decision, reflecting their goals, values, preferences, and desires. [153][154][155][156] There are three areas where SDM has had the greatest impact-food allergy prevention, leveraging the use of the oral food challenge, and food allergy therapy. 155 (Figure 4). AAP, CPS and EAACI guidance. 56,[157][158][159][160][161][162] This approach starkly contrasts to rather prescriptive advice from the turn of the 21st century, which strictly recommended avoidance and left little room for F I G U R E 4 These vignettes represent three possible contexts where a family presents with a diagnostic or management issue that has preference-sensitive care options regarding how to proceed.

Clinical Scenario
A family with a 3-year-old daughter with peanut allergy is concerned about early peanut introduction in their newborn son, who has had some mild eczema since birth The family of a 14-year-old with peanut allergy is considering starting oral immunotherapy or some treatment option, so that she becomes desensitized before entering into her University studies A 15-month-old, who ate peanut for the first time, but did so in the setting of a known RSV infection where she had intermittent fever and cough, developed facial hives which were non-bothersome to the child. The family is seeking peanut allergy skin testing to help determine if the child is allergic

Shared Decision-Making Process
The family is concerned the family history and his eczema make him high risk and that he likely to already have "pre-existing" peanut allergy. They are not sure that it is safe to attempt early introduction either at home or in your office.
The patient has not ingested peanut since she was in kindergarten, which was by accident and resulted in anaphylaxis, which was a traumatic experience. As a result, she has been extremely vigilant in avoiding peanut for many years, limiting her activities, diet (avoiding all products with precautionary labeling) and social interactions to the point that 'life is not much fun'.
The family is seeking peanut testing given they feel the symptoms, though occurring during a documented viral illness, are concerning for peanut allergy. They also remember likely giving him prior tastes of peanut butter, which did not cause reaction when he was well.
Treatment Decision After explaining the early introduction risk factors and reassuring the family that he is standard risk, they agree to forego testing and will try to introduce a peanutcontaining corn puff snack at home. They are comfortable with treating a reaction.
After considering the risks, benefits, and time-commitments, the patient wants to undertake OIT with the aim to decrease her fear of accidental exposures and feel more comfortable in social situations and school activities. She appreciates there is a risk of anaphylaxis as part of the therapy, but believes that the long-term benefits will outweigh the potential risks.
After explaining to the parents that the viral illness could cause urticaria, and that the reaction is not very consistent with allergic urticaria, you agree to order a food challenge as a more definitive test rather than relying on skin testing, which may be misleading in this situation where the history poorly suggests allergy as the cause of the urticaria. consideration of alternative options. 163,164 Moreover, preferencesensitive guidance has been shown to potentially be more costeffective as an added advantage to such an approach. 100,[165][166][167][168] There has been emphasis on SDM with how and when clinicians offer OFCs to their patients. 155 OFC is the gold-standard diagnostic test but has been reluctantly embraced as an office-based tool. 169 Allergists use the OFC to confirm food allergy status, in particular, when there is a low-to-moderate pre-test probability of allergy where even strongly positive skin prick or specific-IgE test lack high enough positive likelihood ratios to shift the posttest odds to definitively rule in allergy. 167 Recognition of such situations allows an opportunity for SDM with offering the OFC, as opposed to performing diagnostic testing. 170 Such may be the case in sensitized children with atopic dermatitis, who are at risk for potential overdiagnosis. 170,171 Use of advanced testing modalities, such as component-resolved diagnostics, BAT, and epitope mapping represent additional considerations to discuss in an SDM paradigm as options to consider with or without OFC, but these must be considered in light of their advantages and disadvantages over traditional testing, with or without the use of OFC. 170 The case of the peanut-allergic child where tree nut sensitization is detected, but the child has never eaten tree nuts represents a perfect setting to invoke SDM to explore options. 170,172 Lastly, with the available therapy options and those in the developmental pipeline, alternatives now exist to how a family can manage food allergy beyond avoidance. 173 New therapies offer significant potential benefits, such as increasing reaction threshold and tempering reaction severity, but have side effects, such as the risk of a potentially severe allergic reaction to the therapy itself, or the development of eosinophilic esophagitis and lifestyle disruption to fit activity restrictions around dosing to prevent potential dose-related symptoms. 101,173,174 SDM is key before committing to a therapy choice so that families are fully informed of the risks, benefits and alternatives. [173][174][175][176] The approach is also valuable for allowing permissive eating in the case of children with high-threshold reactivity, where there may be less benefit or necessity for OIT. 150 Decisionaids have been developed to help assist families with the values clarification process in determining goals and preferences for OIT. 177,178 10 | COMMUNI C ATING WITH PATIENTS IN MIS INFORMED TIME S As discussed throughout this review, there have been many exciting advances in the prevention, diagnosis, and management of food allergies just in the past few years. More than ever, conversations surrounding food allergy require a nuanced understanding of risk and shared decision-making to guide management decisions. Clinicians are tasked with staying up-to-date with current evidence-based information but also must communicate this in a manner understood by patients. With a world of information at their fingertips, patients are seeking advice online and through social media, but the information they find may be outdated, incorrect, or lacking in context. 179 If clinicians wish to remain relevant in their patients' medical decisionmaking, then discussion of these outside influences must be incorporated into clinical practice. 180 F I G U R E 5 Practical tools that can be implemented during clinical encounters to discuss online searches and address misinformation in the office.  and Tweets are often mistaken for evidence. 180 Accounts with large numbers of followers and influencers are given more trust than actual experts, regardless of the accuracy of the information they provide. Individuals often trust those who seem similar to them in their social media groups more than medical professionals, even though they may be strangers or anonymous. 183 Anecdotal stories garner attention and emotional responses although they often lack essential details to help determine if one person's story applies to someone else. Correlation is often confused with causation. Lastly, online 'research' often equates with using common internet search engines to find information supporting one's previously held beliefs while ignoring contradictory information. These influential factors can negatively impact medical decision-making. 184 Many of these problematic occurrences online do not originate from malicious intent but instead reflect the lack of critical thinking skills from users combined with the complex algorithms employed by social media platforms to keep users engaged. 185 Unfortunately, these same tactics can be weaponized, including by those with antiscience agendas or seeking profit from marketing pseudoscientific products or services. 186 Clinicians can help by increasing their own awareness of the many ways online interactions may influence medical decisionmaking. 187